The stimulus-secretion coupling of amino acid-induced insulin release: insulinotropic action of branched-chain amino acids at physiological concentrations of glucose and glutamine.
The stimulant action of branched-chain amino acids upon insulin release was examined in rat pancreatic islets incubated at physiological concentrations of D-glucose and L-glutamine. In the presence of the latter nutrients, L-leucine and L-isoleucine used together at a physiological concentration (0.25 mmol/l each) doubled insulin secretion rate. The effect of L-leucine upon insulin release was dose-related without any indication of of a threshold phenomenon. The insulinotropic action of L-leucine was mimicked, to a limited extent, by its nonmetabolized analogue, 2-aminobicyclo[2,2,1] heptane-2-carboxylic acid. L-Glutamine slightly inhibited glucose-stimulated insulin release. It is concluded that, under close-to-physiological conditions, L-leucine stimulates insulin release by acting in the islet cells both as a fuel and as an allosteric activator of glutamate dehydrogenase.
D000596:Amino Acids / Q000494:pharmacology; D000598:Amino Acids, Cyclic; D000818:Animals; D003470:Culture Media; D004789:Enzyme Activation; D005947:Glucose / Q000494:pharmacology; D005969:Glutamate Dehydrogenase / Q000378:metabolism; D005973:Glutamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007532:Isoleucine / Q000494:pharmacology*; D007930:Leucine / Q000494:pharmacology*; D051381:Rats; D013268:Stimulation, Chemical
D000596:Amino Acids; D000598:Amino Acids, Cyclic; D003470:Culture Media; D007328:Insulin; D007532:Isoleucine; D005973:Glutamine; C006504:2-aminobicyclo(2,2,1)heptane-2-carboxylic acid; D005969:Glutamate Dehydrogenase; D007930:Leucine; D005947:Glucose